Diagnostic device

ABSTRACT

A MANUALLY OPERABLE DIAGNOSTIC DEVICE USEFUL IN MEASURING PROTHROMBIN TIME COMPRISING A HOUSING MEMBER HAVING A SPECIAL RESILIENT CONNECTOR ASSOCIATED THEREWITH AND CONNECTED TO AN AGITATOR EXTENDIBLE WITHIN SAID MEMBER FOR OPERATIVE ENGATEMENT WITH A SAMPLE OF BLOOD OR BLOOD PLASMA CONTAINED THEREBY AND CAPABLE IN OPERA-   TION TO PROVIDE A CLEARLY DISCERNIBLE, AND HENCE READILY DETERMINED MEASURE OF THE PROTHROMBIN TIME OF THE WHOLE BLOOD OR BLOOD PLASMA.

Feb. 2, 1971 M. a. MITTLEMAN DIAGNOSTIC DEVICE Filed Dec. 215, 1968 INVENTOR.

United States Patent 3,560,163 DIAGNOSTIC DEVICE Myron Budd Mittleman, Chicago, Ill., assignor to Armour Pharmaceutical Company, Chicago, 111., a corporation of Delaware Filed Dec. 23, 1968, Ser. No. 786,317 Int. Cl. B01] 11/00; GOln 33/16 US. Cl. 23-253 Claims ABSTRACT OF THE DISCLOSURE A manually operable diagnostic device useful in measuring prothrombin time comprising a housing member having a special resilient connector associated therewith and connected to an agitator extendible within said member for operative engagement with a sample of blood or blood plasma contained thereby and capable in operation to provide a clearly discernible, and hence readily determined measure of the prothrombin time of the Whole blood or blood plasma.

This invention relates generally to the determination of one-stage prothrombin time, partial thromboplastin time and thrombin time for whole blood or blood plasma and more particularly to novel means for making such determinations on relatively small samples of Whole blood or plasma without requiring the presence of sophisticated laboratory or clinical facilities.

As background for the present invention, attention is respectfully directed to my copending application Ser. No. 779,531, filed Nov. 27, 1968, wherein blood coagulation properties and the relationship of prothrombin time to the hemostatic mechanisms of anticoagulant therapy are fully discussed.

As is apparent from the aforesaid discussion, prothrombin time measurements are especially valuable in the treatment of conditions requiring anticoagulant therapy as by the administration of anticoagulant drugs such as dicumarol, heparin, and the like. The administration of these drugs is generally dependent upon and their use controlled primarily by prothrombin time determinations. Thus, the need for quick and accurate means and methods of making such determinations is apparent. In this connection, it should be observed that certain authorities believe that such tests do not measure the level of activity of the prothrombin in the blood, but rather measure the total potential coagulability of the blood. Pragmatically, it is necessary for the physician to know whether the amount of anticoagulant given to a particular patient is adequate to maintain the total coagulability of the blood at such a level that neither spontaneous thrombosis nor hemorrhage will occur. For this purpose the generally utilized measurement is prothrombin time and that term shall be employed in this disclosure to define the period from the formation of thrombin, by the interaction of platelet and plasma components, to the conversion of the fibrinogen to fibrin.

Prothrombin time in normal man is remarkably constant, beinng approximately 12-14 seconds. Thus, deviations, even of one second, may be indicative of a significant abnormality in the patients blood or hemostatic mechanism.

Hematologically, determination of prothrombin time is useful in characterizing the bleeding states due to coagulation defects into two major classes: (I) those with normal prothrombin activity and (II) those with decreased prothrombin activity. Class I comprises the diseases in which, although prothrombin time is entirely normal, the generation of thromboplastin is defective, for example, hemophilia A, hemophilia B, thrombocytopenia, thrombobasthenia and pseudohemophilia B. Class II may be des ignated as the hypoprothrombinemic states, for example, hereditary hypoprothrombinemia vera, hereditary deficiencies of labile and stable factors, annd other defective conditions.

As mentioned in the aforesaid copending application, which introduced to this art, a major step toward simplifying the apparatus needed to make such measurements, measured samples of Whole blood or plasma are mixed in the device with a measured amount of selected reagents, such as thromboplastin containing calcium ions therein. Therefore, the time between reagent engagement to the coagulum is measured by conventional timing means such as a stop watch.

Thus, the need for a device which can measure prothrombin time without requiring hospital or clinical environments for its use, and which can function accurately and well in the absence of auxiliary forms of commercial energy, as expressed in that application, which fulfilled to a major extent by the device described thereby, nonetheless, left some room for even further improvement.

The present invention is based on my design, a device including a novel connector means which provides that improvement.

Specifically, the present invention is predicated upon my design of a device having a simple and unique connector which, when installed between the housing and reciprocative plunger of the device, allows even greater ease of operation and more accuracy of measurement than previously obtained. The device of this disclosure comprises a housing, a reciprocative plunger, and unique connector mean which sealingly connects said plunger to said housing and, in addition thereto, contributes to the strength of the plunger and to the reciprocative action of the plunger relative to the housing.

Accordingly, it is a prime object of the present invention to provide a diagnostic device for use in the measurement of prothrombin time which is inexpensive to manufacture, easy to operate, readily transported and which provides reproducible results concurrently with a patients visit to his physician.

Another object of the present invention is to provide a diagnostic device of the type indicated which permits the measurement of prothrombin time away from hospital and clinical environs, which does not need ancillary equipment, such as centrifuges, constant temperature water baths or other environmental controls to be effective, and which is readily operable even in the absence of gas, electricity and other forms of commercial energy.

A still further object of the present invention is to provide a device of the type indicated in which novel connector means coact to join parts of the device which maintains a sealed compartment for the test and contributing materially to the strength and the reciprocative action of the parts the device relative to each other.

These and still further objects, as shall hereinafter appear, are readily fulfilled by the present invention in a. remarkably unexpected manner as shall be readily discerned from a careful reading of the following detailed description of an exemplary embodiment of the invention, especially when read in conjunction with the accompanying drawing in which:

FIG. 1 is an isomertic view of a device embodying the present invention;

FIG. 2 is a side cross-section of the device of FIG. 1;

FIG. 3 is an enlarged section of the novel connector of this invention apart from the assembled device; and

FIG. 4 is a plan elevation of the connector of FIG. 3.

Referring to the drawing, in which like parts bear like numerals throughout the several views, a diagnostic device, indicated by general reference 10, is shown in FIGS.

1 and 2 and comprises a housing 12 having a bottom 13 which is closed and a mouth 14 which is open. Housing 12 is formed of a transparent material such as plastic, glass or the like and, preferably, is provided with a cylindrical shape. Adjacent mouth 14 the external surface of housing 12 is provided with an upper and a lower annular groove 15 and 16, respectively, which are disposed in circumscribing relationship to housing 12 and in spaced relationship to each other and to the edge of housing 12 defining mouth 14.

A plunger assembly comprising a main shank 21 having an enlargement 22 formed at the upper end thereof and a commingler member 23 disposed at the lower end thereof is insertable within and actuatable for reciprocative action relative to housing 12.

Commingler member 23 may be formed as a relatively flat foraminous plate, either with or without a hollow annulus defined thereabout and extending upwardly therefrom. For purposes of this disclosure, the use of any of the commingler plates already described in my aforesaid copending case Ser. No. 779,531 may be utilized herewith although my current preference is for the commingler design illustrated in FIG. 1 hereof wherein commingler 23 comprises a cylindrical body portion 24 having an open top 25 and a closed bottom 26 which has a number of truncated pie-shaped openings 27 defined therein in spaced relationship to each other and separated by one of a plurality of arms 28 extending radially from a collar 29 which surrounds shank 21.

Collar 29 is affixed to shank 21 at the lower end thereof by any suitable method of fabrication such, for example, as by gluing, forcefitting or the like.

Referring to FIGS. 2 and 3, connector means 31 comprises an outer annular portion 32 having defined on the inner surface 33 thereof a first and second inwardly extending flange 34 and 35, respectively, which are adapted for entry into and seated engagement within grooves 15, 16, to form a sealed engagement therewith.

Connector means 31 further comprises a central portion 36 having an enlarged top or actuator portion 37 into which seating means 38 are defined on the inner surface thereof. Seating means 38 is formed to receive and hold the bulbous portion 22 of shank 21 therebetween. By so connecting actuator portion 37 to plunger 20, external force applied downwardly upon portion 37 is directly transmitted to the plunger 20 which reacts in response thereto as will be explained hereinafter.

Extending downwardly from top portion 37 is elongated sleeve portion 39 which is wrapped around and securely holds about a third of the axial length of shank 21 to provide reinforcement thereof.

A connective portion 40 is operatively disposed between the lower edge of sleeve portion 39 and annular portion 32 and connected therewith to define an inverted generally frustoconical configuration. Connective portion 40 thus completes the sealed relationship of the several parts of my device and by virtue of its relative lack of thickness and the elastic nature of the material from which it is made, coacts in and contributes to the reciprocative movement of plunger 20 relative to housing 12.

When constructed as described, connector means 31 is formed as a unitary structure, preferably molded, and not only possesses a novel and unique structure, it further coacts with plunger 20 and housing 12 to operatively join plunger 20 and housing 12 for reciprocative movement therebetween, it provides reinforcement and strength for the upper portion of shank 21 and it completes the seal of the total assembly.

In practice, connector means 31 is formed of tough but resilient self-sealing materials such, for example, as butyl rubber, gum rubber, rubber and the like, and performs the important function of establishing a set to the device in its at-rest position while providing a biased recoil by virtue of its elastic memory when plunger 20 is 4 free in any other than its at-rest position relative to housing 12.

To assemble a device according to this invention, a plunger 20 is assembled by attaching a commingler 23 to one end of an elongated shank 21 which has an enlarged bulb 22 formed at the other end thereof,

The shank 21 is then inserted up into sleeve portion 39 of a connector 31 until bulb 22 reaches and is engaged in seating means 38.

The plunger-connector sub-assembly next is assembled with a housing 12 by inserting the lower end of plunger 20 into the housing 12 via mouth 14 until annular portion 32 is closely superposed with mouth 14.

Finally, annular portion 32, either by rolling, or otherwise, is brought and stretched in circumscription about housing 12 until flanges 34, 35, respectively, enter and are seated within grooves 15, 16 to complete the sealed construction.

The device, thus assembled, is ready for use for any measurement requiring visible, regulated commingling in a sealed chamber, such as the measurement of prothrombin times, which shall not be described to illustrate the practice.

To operate the device of the invention, the housing chamber is charged with the desired reagents, either at the time of use or previous thereto. Prior charging is preferably effected during the assembly by lyophilizing the desired reagents, such as thromboplastin and calcium chloride in the housing before the connector is mounted thereupon.

Charging at the time of use, which of course, includes the addition of reconstituting fluids to any lyophilized charges employed therein as well as reagents, blood specimens and plasma specimens is readily accomplished byloading the desired charge into a hypodermic and thereafter passing the hypodermic needle through connective portion 40 so that the needle orifice will expel the charge into the housing as it is expressed. The self-sealing quality of the material from which connective portion is fabricated successfully prevents any impurity from entering the housing during the loading procedure. Of course, both the specimen and the reagents are deposited on the floor of the housing 12.

It should be further noted that when the selected reagents are charged and lyophilized in the device substantially prior to the time of use, that to put the device into service, the lyophilized ingredients would first be reconstituted as by the addition of distilled water into the housing chamber in the manner described and prior to the introduction of the blood or plasma specimen.

Immediately after introducing the blood or plasma specimen into the housing and upon effecting an encounter between the specimen and the reagents, a suitable timer, such as a stop watch, is actuated. Thereafter, reciprocation of the plunger 20 is commenced by the action of the operator applying a downward force onto upper portion 37 and thereafter releasing such pressure sufficiently to enable the biasing effective of connective portion 40 to return the plunger to its original position. This action is repeated continuously and with regularity until a coagulum is observed in the bottom of the transparent housing. Upon detection of the coagulum, the timer is stopped and the lapsed time determined.

The procedure described is, of course, equally useful to measure the prothrombin time of normal control blood or plasma as well as that of blood or plasma specimens received from a patient on anticoagulant therapy. It should also be noted that partial thromboplastin time and thrombin time for whole blood or blood plasma may also be performed with my device.

Accurate comparative control data can be also obtained contemporaneously with the determination of the patient, by using the same device and procedures on commercially available normal blood or plasma. In this manner, a standard of comparison is provided from which any deviation of the patients readings can be readily detected.

From the foregoing, it becomes apparent a new and highly useful diagnostic device has been herein described and illustrated which fulfills all of the aforestated 0bjectives in a remarkably unexpected fashion. It is, of course, understood that the embodiments herein described and illustrated are presented to exemplify my invention rather than limit it and that such modifications, applications and alterations as may readily occur to the artisan confronted with this disclosure, are intended Within the spirit of the present invention, especially as it is defined by the scope of the claims appended hereto.

What is claimed is:

1. A diagnostic device for use with a timer to determine certain time-variable properties of a sample of plasma or whole blood, said device comprising a housing for receiving and containing said sample; a reciprocative plunger operatively assembled for axial movement within said housing; and resilient connector means joining said plunger and said housing in sealed relationship therewith, said means including a flexible intermediate portion to bias said plunger in a fixed axial relationship to said housing in its at-rest position and to return said plunger to said fixed axial relationship subsequent to the disruption of said relationship by the application of external force upon said plunger.

2. A device according to claim 1 in which said housing comprises a cylindrical tube closed at one end and having a mouth at the other end thereof, said housing having a pair of spaced parallel grooves defined on the outer surface thereof adjacent said mouth and mating with said connector means to provide a sealing engagement therebetween.

3. A device according to claim 1 in which said plunger comprises an elongated shank and a commingler member attached to an end of said shank and extending outwardly therefrom.

4. A device according to claim 3 in which connector means comprises an outer annular portion stretchable around in sealing engagement with said housing, a sleeve portion extending axially of and wrapped around to hold a portion of said shank, an actuator portion for transmitting externally applied forces to said shank, and a connective portion connecting said annular portion and said sleeve portion and sufficiently elastic to permit without rupture the axial reciprocation of said sleeve portion relative to said annular portion in response to an external force applied to said actuator portion and to return said sleeve portion to a preselected position relative to said annular portion when said external force is removed.

5. A device according to claim 4 in which said commingler member comprises a flat foraminous plate having a peripheral flange extending upwardly therefrom in spaced circumscription to said shaft.

References Cited UNITED STATES PATENTS 2,291,708 8/1942 Gluck 259113 MORRIS O. WOLK, Primary Examiner R. M. REESE, Assistant Examiner U.S. Cl. X.R. 

